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Human Metabolome Database Version 3.5

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Showing metabocard for Leukotriene C4 (HMDB01198)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:10:05 -0700
HMDB ID HMDB01198
Secondary Accession Numbers
  • HMDB06015
Metabolite Identification
Common Name Leukotriene C4
Description Leukotriene C4 (LTC4) is a cysteinyl leukotriene (CysLT), a family of potent inflammatory mediators. Eosinophils, one of the principal cell types recruited to and activated at sites of allergic inflammation, is capable of elaborating lipid mediators, including leukotrienes derived from the oxidative metabolism of arachidonic acid (AA). Potentially 'activated' eosinophils may elaborate greater quantities of LTC4, than normal eosinophils. These activated eosinophils thus are 'primed' for enhanced LTC4 generation in response to subsequent stimuli. Some recognized priming stimuli are chemoattractants (e.g., eotaxin, PAF) that may participate in the recruitment of eosinophils to sites of allergic inflammation. The mechanisms by which chemoattractants and other activating cytokines (e.g., interleukin (IL)-5) or extracellular matrix components (e.g., fibronectin) enhance eosinophil eicosanoid formation are pertinent to the functions of these eicosanoids as paracrine mediators of allergic inflammation. Some eosinophil-derived eicosanoids may be active in down-regulating inflammation. It is increasingly likely that eicosanoids synthesized within cells, including eosinophils, may have intracellular (e.g., intracrine) roles in regulating cell functions, in addition to the more recognized activities of eicosanoids as paracrine mediators of inflammation. Acting extracellularly, the cysteinyl leukotrienes (CysLTs) LTC4 and its extracellular derivatives, LTD4 and LTE4 are key paracrine mediators pertinent to asthma and allergic diseases. Based on their receptor-mediated capabilities, they can elicit bronchoconstriction, mucous hypersecretion, bronchial hyperresponsiveness, increased microvascular permeability, and additional eosinophil infiltration. Eosinophils are a major source of CysLTs and have been identified as the principal LTC4 synthase expressing cells in bronchial mucosal biopsies of asthmatic subjects. (PMID: 12895596 Link_out)Leukotrienes are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes) and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signaling pathways.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. (R-(R*,S*-(E,E,Z,Z)))-N-(S-(1-(4-carboxy-1-hydroxybutyl)-2,4,6,9-pentadecatetraenyl)-N-L-gamma-glutamyl-L-cysteinyl)-Glycine
  2. 5S,6R-Ltc
  3. 5S-Hydroxy,6R-(S-glutathionyl),7E,9E,11Z,14Z-eicosatetraenoate
  4. 5S-Hydroxy,6R-(S-glutathionyl),7E,9E,11Z,14Z-eicosatetraenoic acid
  5. L-gamma-Glutamyl-S-[(1R,2E,4E,6Z,9Z)-1-[(1S)-4-carboxy-1-hydroxybutyl]-2,4,6,9-pentadecatetraenyl]-L-cysteinyl-glycine
  6. Leucotriene C4
  7. Leukotriene C
  8. Leukotriene C1
  9. Leukotriene C4
  10. LTC
  11. LTC4
  12. [R-[R*,S*-(E,E,Z,Z)]]-N-[S-[1-(4-carboxy-1-hydroxybutyl)-2,4,6,9-pentadecatetraenyl]-N-L-gamma-glutamyl-L-cysteinyl]-Glycine 5S,6R-LTC4
Chemical Formula C30H47N3O9S
Average Molecular Weight 625.774
Monoisotopic Molecular Weight 625.303300807
IUPAC Name (5S,6R,7E,9E,11Z,14Z)-6-{[(2R)-2-[(4S)-4-amino-4-carboxybutanamido]-2-[(carboxymethyl)carbamoyl]ethyl]sulfanyl}-5-hydroxyicosa-7,9,11,14-tetraenoic acid
Traditional IUPAC Name (5S,6R,7E,9E,11Z,14Z)-6-{[(2R)-2-[(4S)-4-amino-4-carboxybutanamido]-2-(carboxymethylcarbamoyl)ethyl]sulfanyl}-5-hydroxyicosa-7,9,11,14-tetraenoic acid
CAS Registry Number 72025-60-6
SMILES CCCCC\C=C/C\C=C/C=C/C=C/[C@@H](SC[C@H](NC(=O)CC[C@H](N)C(O)=O)C(=O)NCC(O)=O)[C@@H](O)CCCC(O)=O
InChI Identifier InChI=1S/C30H47N3O9S/c1-2-3-4-5-6-7-8-9-10-11-12-13-16-25(24(34)15-14-17-27(36)37)43-21-23(29(40)32-20-28(38)39)33-26(35)19-18-22(31)30(41)42/h6-7,9-13,16,22-25,34H,2-5,8,14-15,17-21,31H2,1H3,(H,32,40)(H,33,35)(H,36,37)(H,38,39)(H,41,42)/b7-6-,10-9-,12-11+,16-13+/t22-,23-,24-,25+/m0/s1
InChI Key GWNVDXQDILPJIG-NXOLIXFESA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Amino Acids, Peptides, and Analogues
Class Peptides
Sub Class N/A
Other Descriptors
  • Aliphatic Acyclic Compounds
  • Hydroxy Fatty Acids
  • Leukotrienes
  • Organic Compounds
  • Thia Fatty Acids
  • Unsaturated Fatty Acids
Substituents
  • Acyclic Alkene
  • Alpha Amino Acid Or Derivative
  • Carboxamide Group
  • Carboxylic Acid
  • Hydroxyeicosatetraenoic Acid
  • N Acyl Alpha Amino Acid
  • N Acylglycine
  • N Substituted Alpha Amino Acid
  • Primary Aliphatic Amine (Alkylamine)
  • Secondary Alcohol
  • Secondary Carboxylic Acid Amide
  • Thioether
  • Tricarboxylic Acid Derivative
Direct Parent Peptides
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Prostaglandin and leukotriene metabolism
Application Not Available
Cellular locations
  • Extracellular
  • Endoplasmic reticulum
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point Not Available Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 0.0025 g/L ALOGPS
LogP 0.04 ALOGPS
LogP -0.015 ChemAxon
LogS -5.39 ALOGPS
pKa (strongest acidic) 1.8 ChemAxon
pKa (strongest basic) 9.31 ChemAxon
Hydrogen Acceptor Count 10 ChemAxon
Hydrogen Donor Count 7 ChemAxon
Polar Surface Area 216.35 A2 ChemAxon
Rotatable Bond Count 25 ChemAxon
Refractivity 168.51 ChemAxon
Polarizability 68.38 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -2 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations
  • Extracellular
  • Endoplasmic reticulum
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue Location
  • Intestine
  • Skin
  • Platelet
  • Lens
  • Neutrophil
  • Leukocyte
  • Smooth Muscle
Pathways
Name SMPDB Link KEGG Link
Arachidonic Acid Metabolism SMP00075 map00590 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Comments
Blood Detected and Quantified
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4.7E-5 +/- 2.3E-5 uM Adult (>18 years old) Both Normal Not Available
Blood Detected and Quantified
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0.001359 uM Adult (>18 years old) Not Specified Normal Not Available
Blood Detected and Quantified
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0.00006 +/- 0.00003 uM Adult (>18 years old) Both Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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6.989e-05 +/- 2.767e-05 uM Not Specified Not Specified Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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0.000133 +/- 3.454e-05 uM Children (1-13 year old) Not Specified Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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0.000101 uM Not Specified Not Specified Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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7.996e-05 uM Not Specified Not Specified Normal Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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1.791e-05 +/- 4.798e-06 uM Not Specified Not Specified Normal Not Available
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Comments
Blood Detected and Quantified
Article_icon
0.00024 +/- 0.000065 uM Adult (>18 years old) Both Eczema Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
Article_icon
0.000153 +/- 1.711e-05 uM Adult (>18 years old) Not Specified Spinal cord injuries (acute stage) Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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0.000557 uM Not Specified Not Specified AIDS Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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0.000185 +/- 7.628e-05 uM Children (1-13 year old) Not Specified Aseptic meningitis Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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<7.996e-05 uM Not Specified Not Specified closed head Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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1.343e-05 uM Adult (>18 years old) Male glutathione synthetase deficiency, acute metabolic crisis Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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<7.996e-05 uM Not Specified Not Specified gunshot wound Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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0.000422 uM Not Specified Not Specified HIV positive Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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2.399e-05 uM Not Specified Not Specified HIV-Seropositive, Dementia Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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<0.000160 uM Not Specified Not Specified hydrocephalus Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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0.00413 +/- 0.000611 uM Not Specified Not Specified subarachnoid hemorrhage with cerebral vasospasm Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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0.000280 uM Not Specified Not Specified HIV-Seropositive (Neurologically normal) Not Available
Cerebrospinal Fluid (CSF) Detected and Quantified
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0.00130 +/- 0.000227 uM Not Specified Not Specified subarachnoid hemorrhage without cerebral vasospasm Not Available
Associated Disorders and Diseases
Disease References
Eczema
  • Hua Z, Fei H, Mingming X: Evaluation and interference of serum and skin lesion levels of leukotrienes in patients with eczema. Prostaglandins Leukot Essent Fatty Acids. 2006 Jul;75(1):51-5. Epub 2006 Jun 6. Pubmed: 16757158 Link_out
    Associated OMIM IDs
    DrugBank ID Not Available
    Phenol Explorer Compound ID Not Available
    Phenol Explorer Metabolite ID Not Available
    FoodDB ID FDB022484
    KNApSAcK ID Not Available
    Chemspider ID 4444133 Link_out
    KEGG Compound ID C02166 Link_out
    BioCyc ID LEUKOTRIENE-C4 Link_out
    BiGG ID 2212273 Link_out
    Wikipedia Link Leukotriene C4 Link_out
    NuGOwiki Link HMDB01198 Link_out
    Metagene Link HMDB01198 Link_out
    METLIN ID 3681 Link_out
    PubChem Compound 5280493 Link_out
    PDB ID Not Available
    ChEBI ID 16978 Link_out
    References
    Synthesis Reference Rokach, Joshua; Young, Robert N.; Kakushima, Masatoshi; Lau, Cheuk-Kun; Seguin, Rick; Frenette, Richard; Guindon, Yvan. Synthesis of leukotrienes. New synthesis of natural leukotriene A4. Tetrahedron Letters (1981), 22(11), 979-82.
    Material Safety Data Sheet (MSDS) Download (PDF)
    General References
    1. Sawazaki Y: [Leukotriene B4, leukotriene C4 and prostaglandin E2 in the serum, synovial fluid and synovium in patients with rheumatoid arthritis] Nippon Ika Daigaku Zasshi. 1989 Dec;56(6):559-64. Pubmed: 2558123 Link_out
    2. Heimburger M, Palmblad JE: Effects of leukotriene C4 and D4, histamine and bradykinin on cytosolic calcium concentrations and adhesiveness of endothelial cells and neutrophils. Clin Exp Immunol. 1996 Mar;103(3):454-60. Pubmed: 8608646 Link_out
    3. Lane SJ, Lee TH: Mast cell effector mechanisms. J Allergy Clin Immunol. 1996 Nov;98(5 Pt 2):S67-71; discussion S71-2. Pubmed: 8939179 Link_out
    4. Romero R, Wu YK, Mazor M, Hobbins JC, Mitchell MD: Increased amniotic fluid leukotriene C4 concentration in term human parturition. Am J Obstet Gynecol. 1988 Sep;159(3):655-7. Pubmed: 3421265 Link_out
    5. Paoletti P, Gaetani P, Grignani G, Pacchiarini L, Silvani V, Rodriguez y Baena R: CSF leukotriene C4 following subarachnoid hemorrhage. J Neurosurg. 1988 Oct;69(4):488-93. Pubmed: 3418380 Link_out
    6. De Servi S, Ricevuti G, Mazzone A, Pasotti D, Bramucci E, Angoli L, Specchia G: Transcardiac release of leukotriene C4 by neutrophils in patients with coronary artery disease. J Am Coll Cardiol. 1991 Apr;17(5):1125-8. Pubmed: 2007712 Link_out
    7. Koshino T, Takano S, Houjo T, Sano Y, Kudo K, Kihara H, Kitani S, Takaishi T, Hirai K, Ito K, Morita Y: Expression of 5-lipoxygenase and 5-lipoxygenase-activating protein mRNAs in the peripheral blood leukocytes of asthmatics. Biochem Biophys Res Commun. 1998 Jun 18;247(2):510-3. Pubmed: 9642160 Link_out
    8. Richter L, Hesselbarth N, Eitner K, Schubert K, Bosseckert H, Krell H: Increased biliary secretion of cysteinyl-leukotrienes in human bile duct obstruction. J Hepatol. 1996 Nov;25(5):725-32. Pubmed: 8938552 Link_out
    9. Sternfeld M, Fink A, Bentwich Z, Eliraz A: The role of acupuncture in asthma: changes in airways dynamics and LTC4 induced LAI. Am J Chin Med. 1989;17(3-4):129-34. Pubmed: 2633615 Link_out
    10. Ponicke K, Forster W: Influence of leukotriene C4 on aggregation and on malondialdehyde formation of human blood platelets. Biomed Biochim Acta. 1984;43(8-9):S459-62. Pubmed: 6440558 Link_out
    11. Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD: Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005 Feb;67(2):545-57. Epub 2004 Nov 10. Pubmed: 15537867 Link_out
    12. Sjolinder M, Tornhamre S, Claesson HE, Hydman J, Lindgren J: Characterization of a leukotriene C4 export mechanism in human platelets: possible involvement of multidrug resistance-associated protein 1. J Lipid Res. 1999 Mar;40(3):439-46. Pubmed: 10064732 Link_out
    13. Angi MR, Bettero A, Filippi F, Salvalaio L, Benassi CA: [Quantitative evaluation of conjunctival irritation by simultaneous determination of histamine, serotonin and leukotriene C4 in tears] Ophtalmologie. 1987 Oct-Dec;1(4):509-11. Pubmed: 3153930 Link_out
    14. Cruz JR, Cano F, Razin E, Acheson DW, Keusch GT: Fecal excretion of leukotriene C4 during human disease due to Shigella dysenteriae. J Pediatr Gastroenterol Nutr. 1995 Feb;20(2):179-83. Pubmed: 7714683 Link_out
    15. Zijlstra FJ, Wilson JH: 15-HETE is the main eicosanoid present in mucus of ulcerative proctocolitis. Prostaglandins Leukot Essent Fatty Acids. 1991 May;43(1):55-9. Pubmed: 1652771 Link_out
    16. Matsumoto S, Hayashi Y, Kinoshita I, Ikata T, Yamamoto S: Immunoaffinity purification of prostaglandin E2 and leukotriene C4 prior to radioimmunoassay: application to human synovial fluid. Ann Clin Biochem. 1993 Jan;30 ( Pt 1):60-8. Pubmed: 8434868 Link_out
    17. Talbot SF, Atkins PC, Goetzl EJ, Zweiman B: Accumulation of leukotriene C4 and histamine in human allergic skin reactions. J Clin Invest. 1985 Aug;76(2):650-6. Pubmed: 2411760 Link_out
    18. Kloprogge E, de Leeuw AJ, de Monchy JG, Kauffman HF: Cellular communication in leukotriene C4 production between eosinophils and neutrophils. Int Arch Allergy Appl Immunol. 1989;90(1):20-3. Pubmed: 2509375 Link_out
    19. Damtew B, Spagnuolo PJ: Leukotriene C4 from vascular endothelium enhances neutrophil adhesiveness. Prostaglandins Leukot Essent Fatty Acids. 1997 Feb;56(2):111-6. Pubmed: 9051719 Link_out
    20. Schauer U, Eckhart A, Muller R, Gemsa D, Rieger CH: Enhanced leukotriene C4 production by peripheral eosinophilic granulocytes from children with asthma. Int Arch Allergy Appl Immunol. 1989;90(3):201-6. Pubmed: 2512259 Link_out
    Enzymes
    Name: Gamma-glutamyltranspeptidase 1
    Reactions:
    • (5-L-glutamyl)-peptide + an amino acid = peptide + 5-L-glutamyl amino acid [RN:R04159]
    Gene Name: GGT1
    Uniprot ID: P19440 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    Name: Leukotriene C4 synthase
    Reactions:
    • leukotriene C4 = leukotriene A4 + glutathione [RN:R03059]
    Gene Name: LTC4S
    Uniprot ID: Q16873 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    Name: Gamma-glutamyltransferase 6
    Reactions:
    • (5-L-glutamyl)-peptide + an amino acid = peptide + 5-L-glutamyl amino acid [RN:R04159]
    Gene Name: GGT6
    Uniprot ID: Q6P531 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    Name: GGT7 protein
    Reactions:
      Gene Name: GGT7
      Uniprot ID: A0PJJ9 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Gamma-glutamyltransferase 5
      Reactions:
        Gene Name: GGT5
        Uniprot ID: P36269 Link_out
        Protein Sequence: FASTA
        Gene Sequence: FASTA
        Transporters
        Name: Multidrug resistance-associated protein 1
        Reactions:
          Gene Name: ABCC1
          Uniprot ID: P33527 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA